Innovations in Cancer Treatment of

Children
Lauren Helms, MD,a,* Allison E. Guimera, MD,b,* Katherine A. Janeway, MD,c Kelly M. Bailey, MD, PhDd

Pediatric cancer outcomes have significantly improved, and yet this success is not abstract
spread equally across cancer types or patients. Disparities data in pediatric oncol-
ogy highlight needed improvements in access to care, including clinical trials and
advanced testing for all patients. For cancers such as brain tumors and sarcomas,
continued advancement in understanding the biology of tumor heterogeneity is
an essential step toward finding new therapeutic combinations to improve out-
comes. Pediatric cancer survivors need access to emerging technologies aimed at
reducing or better managing toxicities from therapy. With advances in treatment
and survival, pediatric oncology patients continue to need longitudinal, multidisci-
a
plinary subspecialty care. Refining the communication between pediatric oncolo- Department of Pediatrics, Michigan Medicine, Ann Arbor,
Michigan; bDepartment of Pediatrics, University of
gists, primary pediatricians, survivorship clinics, and adult primary care is key in California Los Angeles, Los Angeles, California;
c
ensuring the best lifelong care of pediatric cancer survivors. In this State-of-The- Dana-Farber/Boston Children’s Cancer and Blood
Disorders Center, Boston, Massachusetts; and dDivision of
Art review, we discuss 5 major domains in pediatric oncology: reducing toxicity, Pediatric Hematology and Oncology, Department of
cancer biology, novel therapies, detection and monitoring, and access to care, to Pediatrics, University of Pittsburgh School of Medicine,
Pittsburgh, Pennsylvania
highlight recent advances and areas for continued improvement.
Drs Helms and Guimera contributed to the manuscript
draft and figure editing; Drs Janeway and Bailey
conceptualized the article and contributed to the
In the past 50 years, pediatric cancer outcomes have greatly improved. Some can- manuscript draft; and all authors critically reviewed
and revised the manuscript, approved the final
cers, such as pediatric acute lymphoblastic leukemia, have demonstrated steady manuscript as submitted, and agree to be accountable
improvements in outcome throughout this time, with a 3-year survival in 1975 of for all aspects of the work.
59% and a 5-year survival in 2020 of 90%.1–4 Immunotherapy continues to *Contributed equally as co-first authors.
revolutionize the treatment of aggressive pediatric leukemias and lymphomas.5,6 DOI: https://doi.org/10.1542/peds.2023-061539
In contrast, after initial improvements in outcome because of the discovery and Accepted for publication Jul 24, 2023
use of chemotherapeutic agents such as doxorubicin and pediatric cancers such
Address correspondence to Kelly M. Bailey, MD, PhD, UPMC
as bone sarcomas, some brain tumors have not achieved meaningful survival im- Children’s Hospital of Pittsburgh, 5122 Rangos Research
provements with new therapies in decades.7 Broadly speaking, survival differ- Building, 4401 Penn Ave, Pittsburgh, PA 15224. E-mail:
kelly.bailey@chp.edu
ences have inspired 2 major research focuses in pediatric oncology: (1) for
PEDIATRICS (ISSN Numbers: Print, 0031-4005; Online,
patients with excellent (90%1) survival, we now seek ways to reduce or modify 1098-4275).
therapy to minimize long-term treatment complications, and (2) for patients diag- This is an open access article distributed under the terms of the
nosed with tumors stuck in a survival “plateau” (continued poor outcomes), we Creative Commons Attribution-NonCommercial-NoDerivatives 4.0
International License (https://creativecommons.org/licenses/
turn to innovations in biology to determine new therapeutic vulnerabilities, en- by-nc-nd/4.0/), which permits noncommercial distribution and re-
hance disease monitoring, and better understand tumor heterogeneity, metastasis, production in any medium, provided the original author and
source are credited.
and treatment resistance.
Primary pediatricians are often the physicians first uncovering the atypical FUNDING: Dr Bailey is currently supported by the
National Institutes of Health (NCI K08CA252178) and
symptoms, abnormal physical exam findings, and concerning laboratory values would like to thank the UPMC Children’s Hospital
that ultimately lead to the workup and diagnosis of cancer in children. Sus- Foundation for their support. The other authors
received no additional funding.
pected malignant solid tumors in children most often require a biopsy to deter-
CONFLICT OF INTEREST DISCLOSURES: Dr Janeway has
mine a definitive diagnosis. Historically, the majority of these diagnostic served as a consultant for Bayer, Ipsen, and Illumina;
biopsies were open biopsies performed by pediatric or orthopedic surgeons. the other authors have indicated they have no potential
conflicts of interest to disclose.
Given innovations in image-guided percutaneous biopsy techniques, diagnostic
tumor core biopsies are performed by interventional radiologists and at many
institutions are now more common than open biopsies.8 Tumor molecular To cite: Helms L, Guimera AE, Janeway KA, et al.
Innovations in Cancer Treatment of Children.
profiling at the time of diagnosis is also now more prevalent and helps drive Pediatrics. 2023;152(6):e2023061539
personalized medicine efforts in pediatric oncology.9,10

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 PEDIATRIC CANCER TREATMENT TODAY: WHAT DOES IT LOOK
LIKE?
Although some children with specific subtypes of cancer
have benefitted from targeted therapies or immunothera-
pies, the vast majority of children diagnosed with cancer
today are still treated with standard chemotherapy and
sometimes surgery and/or radiation therapy. As more chil-
dren survive pediatric cancer, primary care pediatricians
and pediatricians across subspecialties increasingly inter-
act with childhood cancer survivors, children living with
cancer, and their families (Fig 1). Pediatric cancer affects
almost every facet of child and adolescent health. This
State-of-the-Art article aims to provide pediatricians with
an update on the state of pediatric cancer care. We high-
light the following domains: reducing toxicity, cancer biol-
ogy, novel therapies, detection and monitoring, and access
to care, because these domains both represent areas of
need for children with cancer and core topics in general
pediatric medicine, such as long-term health, medical re-
search and advancement, and health disparities.
REDUCING TOXICITY
Thanks to cooperative national clinical trial efforts over
decades, some pediatric patients diagnosed with cancer,
such as newly diagnosed standard risk B-cell lympho-
blastic leukemia, now have excellent outcomes (>90%
Reducing
Toxicity
Detection and
Monitoring
Biology
FIGURE 1
Overview of 5 major areas of advancement in pediatric oncology. Figures created with BioRender.com.
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event-free and overall survival).11 Despite these excellent
outcomes, current treatment regimens result in signifi-
cant risk of both short-term (during therapy) and long-
term (after therapy completion) side effects, and many
pediatric cancer survivors are diagnosed with 1 or more
chronic health issues.12–14 In the setting of overall excel-
lent outcomes, a logical next-step is to determine how to
better mitigate or treat toxicities while maintaining ex-
cellent overall survival. Table 1 highlights examples of
only some of the toxicities encountered during cancer di-
rected therapy to highlight the range of approaches to re-
duce or avoid those long-term effects. These approaches
include future lifestyle modifications, protective medica-
tions, utilizing different chemotherapy regimens, and
broadly reducing exposure to agents by optimizing risk
stratification (what patients can still have excellent out-
comes with less chemotherapy or radiation exposure).
Therapy Reduction
One approach to toxicity reduction is decreasing cumula-
tive doses of chemotherapy. Again, using leukemia as an
example, chemotherapy is assigned by risk group. Pa-
tients with standard risk leukemia are exposed to less
cumulative anthracyclines as compared with patients
with high-risk leukemia.15,16 Further, historically boys re-
ceived an additional year of maintenance chemotherapy
for the treatment of B-cell lymphoblastic leukemia on
Novel
Therapies
Access to
Care
 TABLE 1 Examples of Long-term Side Effects From Pediatric Cancer Treatment and Interventions
Examples of Long-term Side Effects From
Cancer Type Therapy63–66
Hodgkin lymphoma  Gonadal dysfunction: potential for reduced
fertility or infertility in both males and females
 Thyroid complication: hypothyroidism;
increased risk of thyroid cancer
Acute lymphoblastic leukemia  Growth impairment including short stature,
precocious puberty, or delayed puberty
 Metabolic syndrome, obesity
Neuroblastoma  Hearing loss: related to exposure to platinum
compounds
 Cataracts
Wilms tumor  Cardiac toxicity: related to anthracyclines,
radiation involving heart
 Renal dysfunction: glomerular and tubular
damage; end-stage renal disease in patients
with bilateral Wilms tumor or receiving
radiation therapy in unilateral disease
Examples of Interventions to Reduce
Long-term Side Effects63–66
 Discussing options for fertility preservation
at diagnosis and during long-term follow-up
visits
 Thyroid complications: decreased risk by
reducing utilization of radiation therapy
 Growth impairment: improved by the
replacement of cranial radiotherapy with
intrathecal chemotherapy
 Dietary and exercise interventions
 Reduce the duration and intensity of
treatment when possible through risk
stratification efforts
 Cardiac toxicity: using cardioprotective agents
(dexrazoxane), and minimizing chemotherapy
and radiation when possible
 Renal dysfunction: nephron-sparing surgery
for bilateral disease, avoiding nephrotoxic
agents (for example, non-steroidal anti-
inflammatories)

some cooperative treatment protocols. Current practice
has eliminated this extra year of therapy for boys as with
modern upfront intensive treatment regimens, the risks
of this practice outweigh the benefits.17 Reduction or
elimination of radiation therapy is another example of
therapy modifications that can reduce late effects such as
secondary malignancies. Recent data have demonstrated
that radiation therapy can be eliminated for patients
with Hodgkin lymphoma that demonstrate adequate re-
sponse to chemotherapy.18
Less Toxic Treatments
New chemotherapy formulations aimed at maintaining
antitumor activity while reducing damage to normal tissue
are emerging. Liposomal formulations of chemotherapy,
such as doxorubicin, are in various stages of preclinical
testing and clinical trials. In addition to less toxic formula-
tions of traditional chemotherapy, immunotherapies have
emerged as treatments with reduced—or different—toxicity
profiles as compared with DNA damage directed chemo-
therapies. To date, immunotherapies have been most
successful in the treatment of pediatric leukemias and lym-
phomas, and the long-term toxicity profiles of these treat-
ments continue to be examined.19–21
Pharmacogenomics
Large sequencing efforts in pediatric oncology over the
past decade have greatly enhanced understanding of
germline alterations in children with cancer.22–24 This is
important not only for cancer predisposition and tumor
biology but also for the way in which a child’s genetic
make-up may alter how they metabolize drugs. Such
pharmacogenomic analyses may reveal the need to dose
reduce certain medications or prompt the use of certain
drugs in patients demonstrating genetic factors that may
make a medicine more efficacious. As 20% of children
with cancer will be admitted to the hospital for the treat-
ment of an adverse drug reaction,25 this is an emerging
area of importance given the steady rise in patient access
to tumors and germline sequencing. Further, early pre-
diction of patients whose tumors may not respond to a
drug could help physicians consider alternatives earlier.
One example of this is response to platinum agents being
reduced by mutations in genes of the ERCC family of
DNA excision repair proteins.25
Onco-fertility
Until new treatment options emerge, some side effects
are currently unavoidable, such as the likelihood of some
treatments affecting fertility. Patients experiencing life-
threatening oncologic medical emergencies often do not
have time to undergo fertility preservation before initia-
tion of gonadotoxic treatments. Cumulative exposure to
cyclophosphamide and equivalent drugs greatly reduces
a child’s future ability to have children.26,27 Postpubertal
females and males have the option for pretreatment oo-
cyte or sperm cryopreservation.28 Recent advances in
fertility preservation have emerged and provide a way to
enhance chances of future fertility while still successfully
treating a child’s cancer. For example, prepubertal fe-
males at some specialized centers now have access to re-
search protocols attempting ovarian cryopreservation for
fertility preservation.29,30 Infertility can have a major im-
pact on an adult’s quality of life. Continued advances in

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 fertility preservation—and affordable, reliable access to
fertility counseling and preservation services—have the
potential to significantly improve the long-term well-
being of children and adolescents with cancer.31
Long-term Survivorship
Pediatric oncology patients routinely follow-up in survivor-
ship clinics annually after completion of initial therapy and
undergo active disease surveillance for a number of years.
Predicted side effects from therapy are monitored over
time. Efforts to optimize communication with primary care
pediatricians and include pediatricians as an active mem-
ber of the postcancer care team is a priority. Patients and
families often move or re-establish care and, therefore, ef-
forts have focused on establishing survivorship portals
that can “move” with the patient.32 A wealth of educational
information and care guidelines are also provided, www.
survivorshipguidelines.org.33 Accurate and up to date com-
munication regarding the overall health monitoring of sur-
vivors is also needed to ensure the successful transition to
adult medicine care. Awareness and monitoring are key
components to successful management of long-term toxic-
ities for childhood cancer survivors (Fig 2).
BIOLOGY: UNDERSTANDING AGGRESSIVE TUMOR
SUBPOPULATIONS
An unfortunate reality of pediatric cancer is that some chil-
dren still do not survive. Children diagnosed with brain tu-
mors such as diffuse intrinsic pontine glioma (DIPG) and
bone tumors such as osteosarcoma and metastatic Ewing
sarcoma have not seen meaningful improvements in out-
comes in decades. For these cancers, researchers strive to
continue to better understand the biology of these tumors
(heterogeneity, metastatic potential, immune evasion, treat-
ment resistance, and stemness—a cancer cell’s ability to
undergo “self-renewal and differentiation”34) and corre-
sponding interventions that may “move the needle” toward
improving survival. As these cancer types are less common
than pediatric leukemias, some of the challenges in under-
standing these tumors derives from the fact that they are
relatively rare, thereby making tumor subpopulations more
challenging to study.
Risk Groups
For cancers with >50% survival at diagnosis such as bone
sarcomas, a logical question to ask is: what biologic fea-
tures make some primary tumors more aggressive than
others? Pediatric sequencing efforts have clearly demon-
strated the genetic profiles across the spectrum of pediatric
cancers. Tumor subsets exist and there is a clear need to
understand which tumor subsets are associated with infe-
rior clinical outcomes. Aggressive tumor subtypes can then
be studied to determine specific vulnerabilities, and ulti-
mately provide clues to new treatments to test in patients
with aggressive tumor subtypes. Neuroblastoma is an ex-
ample of a solid tumor where ALK mutations and N-Myc
amplification have been found to drive cancer progression
and be associated with worse outcomes.35,36 ALK inhibitors
(eg, crizotinib, lorlatinib, etc) are being studied in the treat-
ment of ALK mutated high risk neuroblastoma, an example

transition to adult
primary pediatrician
care

-coping
-cancer genetics
child and siblings -well child checks
-concerning survivorship care plan
symptoms or
physical exam
ndings
active survivorship
-abnormal labs or cancer therapy
imaging results surveillance clinic
child diagnosed
with cancer pediatric oncologist

additional pediatric subspecialty care

FIGURE 2
Overview of care transitions and collaborations for children with cancer. A child and their siblings (if applicable) receive primary pediatric
care. When a primary pediatrician notes abnormal symptoms, etc and a child is diagnosed with cancer, care shifts to the pediatric oncology
team. After therapy, the child with cancer transitions back to their primary pediatrician and both short- and long-term survivorship care
plans are developed.

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 of biologic understanding driving treatment change.37 Dedi-
cated efforts for defining risk groups for bone sarcomas are
underway.
Disease Modeling
Before any compound being tested in clinical trials, pre-
clinical testing is needed. Although cell lines are often
useful for dissecting the effects of a compound on signal-
ing pathways, cell lines often poorly mimic the complex-
ity of the in vivo tumor microenvironment. With current
preclinical models of many pediatric cancers, it is still
challenging to predict clinical effectiveness of an agent.38
We strive to use patient derived xenografts and immuno-
competent models of cancer and to represent tumor sub-
sets in preclinical studies. Advances in the generation of
humanized mice (mice transplanted with human immune
cells) allows investigators to now better understand the
complex relationships between the tumor and the body’s
immune system. Given the rise in immunotherapeutic ap-
proaches to cancer treatment in the past decade, immu-
nocompetent modeling is a key emerging component in
studying the efficacy of specific immunotherapies.39
Samples for Research
For rare tumors, every sample is valuable. National and in-
ternational efforts to enhance biospecimen banking of diffi-
cult to treat cancers is a priority. The field continues to
rely on the generosity and willingness of pediatric patients
and their families to participate in research studies to ad-
vance our understanding of these cancers.40 Optimizing
sample storage conditions and annotation through data
harmonization is an ongoing priority. For cancers such as
DIPG, biopsy samples were historically not obtained and
diagnosis was made based on clinical or MRI findings
alone. Recent advances in neurosurgical stereotactic biopsy
approaches now provide an opportunity for biopsy mate-
rial from suspected DIPGs to be safely obtained.41 Such di-
agnostic biopsy material allows for a richer understanding
TABLE 2 Examples of Targeted Agents for the Treatment of Pediatric, Adolescent, and Young Adult Cancers
Cancer Type Example of Actionable Target35,46,47,67–73
Acute lymphoblastic leukemia  Expression of CD19
Infantile fibrosarcoma  NTRK fusion
Neuroblastoma  High expression of GD2
 ALK mutation
Low grade gliomas  BRAF mutations
Hodgkin lymphoma  CD30
Mature B cell lymphomas  CD20
Epithelioid sarcoma  SMARCB1/INI1 mutations
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of DIPG biology and researchers hope such samples will
start to provide clues for new therapeutic approaches.
In addition to obtaining material at the time of original
diagnostic biopsies, biopsy material at the time of relapse
is also invaluable. Tumors change over time and after ex-
posure to cytotoxic chemotherapy. Individual tumor subpo-
pulations can develop resistance, ultimately resulting in
disease relapse.42,43 Historically, pediatric cancers were
not always biopsied at the time of relapse to spare chil-
dren from additional procedures. Given the need to better
understand relapsed disease to improve outcomes and the
ability to participate in clinical trials, for example, the Na-
tional Cancer Institute-Children’s Oncology Group Pediatric
MATCH trial (“matching” tumor alterations to possible tar-
geted therapy), there has been a shift in practice and to-
day, pediatric patients are more likely to be offered
rebiopsy at the time of suspected disease progression.44
The MATCH trial has demonstrated the feasibility of identi-
fying personalized therapeutic options for pediatric pa-
tients with difficult to treat cancer.45
NOVEL THERAPIES
New treatment approaches are needed to continue to im-
prove upon long-term morbidity and mortality for pedi-
atric patients with cancer. Examples of targeted agents
(antibodies, cellular therapies, kinase inhibitors, anti-
body-drug conjugates, etc) used in the treatment of pedi-
atric cancer are listed in Table 2.
Precision Oncology
The goal of precision oncology is to identify drugs pre-
dicted to work against tumors with specific mutations,
etc. As noted above, The MATCH trial has demonstrated
the feasibility of identifying personalized therapeutic op-
tions for pediatric patients with difficult to treat can-
cer.45 Examples of recent precision oncology success
stories in pediatric oncology include the utilization of
NTRK inhibitors for rare NTRK pediatric solid tumors,
Example Targeted Agents35,46,47,67–73
 Blinatumomab (CD19-CD3 bispecific T-cell engager, BiTE)
 CD19 chimeric antigen receptor (CAR) T cells
 NTRK inhibitors (larotrectinib, etc)
 Dinutuximab (monoclonal antibody against GD2)
 ALK inhibitors (lorlatinib, etc)
 RAF inhibitors, pan-RAF inhibitors (tovorafenib), and MEK
inhibitors
 Brentuximab vedotin (CD30 targeting antibody drug
conjugate. Chemotherapy agent linked to CD30 is
monomethyl auristatin E [MMAE])
 Rituximab (CD20 chimeric antibody)
 Tazemetostat (EZH2 inhibitor)
5
 such as infantile fibrosarcoma and RAF/MEK inhibitors
for the treatment of low-grade gliomas in children.46–48
Age of Immunotherapies
Hundreds of immunotherapies for the treatment of cancer
now exist. Broadly, these therapies include engineered
cells, such as CD19 CAR-T cells for the treatment of pediat-
ric B-cell lymphoblastic leukemia, checkpoint inhibitors
aimed at “reawakening” the body’s own immune system,
cytokine manipulation, and agents aimed at remodeling
the tumor microenvironment. Although challenges exist in
the utilization of CAR-T cells for the treatment of solid tu-
mors, exciting progress has been made in demonstrating
the feasibility of CAR-T cell utilization for the treatment of
currently incurable pediatric cancers such as DIPG (diffuse
intrinsic pontine glioma).49 Given the rapid rise in immu-
notherapies being developed in adults, there is significant
future potential in immunomanipulation for the treatment
of pediatric cancers. Currently, few children with cancer
are treated with immunotherapies. In addition, we are
only beginning to understand the long-term side effects of
immunomanipulation on the health of children and adoles-
cents. As these data emerge, continued communication
with general pediatricians is essential to ensure that these
effects are recognized and effectively addressed.
Combination Approaches
Tumors are known to be heterogeneous and develop
treatment resistance, including resistance to targeted
agents. Tumors rarely demonstrate long-term responses
to single agents. Combination approaches to “attack” tu-
mors using different methods is one way to circumvent
the resistance. Combining DNA damaging agents with im-
munotherapies and utilizing antibody-drug conjugates
are 2 examples of emerging multimodality therapies that
have the potential to continue to change the landscape of
pediatric cancer treatment. Immunotherapy timing (the
delivery order of agents and/or severity of immunosup-
pression when agents are given) is especially critical
when adding immunotherapies to existing treatment reg-
imens. Preclinical data specifically addressing immuno-
therapy timing is an emerging topic of great interest.50,51
DETECTION AND MONITORING
Disease monitoring is conducted both on-therapy and af-
ter completion of initial therapy for the treatment of can-
cer in children. Child exposure to radiation, such as that
delivered by chest radiographs and CT scans, should al-
ways be avoided or minimized when possible. New tech-
nologies are emerging that likely will revolutionize the
way tumor responses and relapses are monitored.
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ctDNA
When tumor cells die, fragments of DNA from the tumor
cells are released into the bloodstream of the patient. This
circulating tumor DNA (ctDNA) can be detected in blood
from patients with cancer52 and provides many future op-
portunities: (1) more frequent monitoring of disease re-
lapse at a level that a scan may not be able to detect,
(2) reduce exposure to radiation, and (3) detect emerg-
ing resistant subpopulations of tumor cells while on
therapy. One large question that ctDNA may be able to
help address is whether earlier detection and treatment
of relapses will improve outcomes. As ctDNA monitoring
(“liquid biopsies”) is increasingly included on prospective
clinical trials, we will come to more fully understand the
potential of this technology. A recent example of the power
of ctDNA was demonstrated in intermediate risk, fusion
negative rhabdomyosarcoma, where investigators demon-
strate that the presence of ctDNA in a patient’s serum at di-
agnosis is associated with a worse outcome (statistically
significant inferior event-free and overall survival).53
Germline Findings
In addition to tumor sequencing, germline sequencing of pe-
diatric patients with cancer has also increased and can com-
plement and enhance knowledge derived from tumor-only
sequencing.54,55 As discussed above, there may be potential
pharmacogenomic benefits of this information. Additionally,
should a patient have a germline pathogenic variant in a
cancer predisposition gene discovered, cancer screening rec-
ommendations may be suggested for the patient.56,57 We
know that some children develop secondary malignancies
after their primary cancer therapy. We still do not fully un-
derstand which pathogenic germline findings may increase
the likelihood of children developing a treatment-related
secondary malignancy. Family members of children with
cancer may be referred for genetic counseling and testing
depending on the germline result found in the child. Many
variants of unknown significance are detected during germ-
line testing, and as more data emerge, screening and risk
recommendation are updated over time. It is especially im-
portant to remember this for survivors who may not have
had access to germline testing when initially diagnosed or
treated, as they may desire testing. If testing did occur, a re-
examination of the interpretation of the findings may be
warranted given variant reclassifications over time. Many
children’s hospitals nationally now have cancer predisposi-
tion programs where referrals for genetic counseling and
testing are accepted both for patients with cancer and their
family members.58
ACCESS TO CARE
Pediatricians are well aware that inequities in access to
care exist. Pediatric oncology is not spared from this
reality.
 DATA ON DISPARITIES
In the United States, Black children diagnosed with can-
cer continue to have inferior overall survival compared
with white children. One example of many is that lower
survival rates are observed among Black children with
acute myeloid leukemia when compared with non-Hispanic
white children.59 The reasons for this are understudied
and multifactorial, though minority populations remain
underrepresented in cancer research.59 Rates of relapse
among minority children and those living in poverty
also remain higher across disease groups,59 highlighting
the need for social determinants of health to be incorpo-
rated into treatment plans. Globally, overall survival for
children with cancer varies based on the income status
of the country in which they reside. Issues with access
to cancer drugs, clinical trials, expert opinions for rare
tumors, supportive care measures, and advanced testing
such as tumor sequencing all contribute to the noted
disparities.59,60
When considering clinical trials, an emerging approach
in oncology is the integrated use of real-world data
(RWD) or real world evidence. Although randomized con-
trol trials are the gold standard in pediatric oncology, for
rare tumors and understanding subpopulations of pa-
tients, this is not always feasible. Examples of RWD in-
clude electronic medical record data, billing data, social
media platforms, patient or family surveys, and informa-
tion from tumor registries. For example, use of real world
evidence helped lay the groundwork for the accelerated
US Food and Drug Administration approval of blinatumo-
mab for the treatment of relapsed or refractory B cell
acute lymphoblastic leukemia in adults.61 Incorporation of
RWD may help bridge some gaps in disparities in clinical
trial access and more timely access to emerging drugs in
pediatric oncology.
For survivors, access to specialty services, such as phys-
ical and occupational therapy, ongoing oncofertility and
reproductive health resources, neuropsychologic testing,
and behavioral health services are inconsistent. For exam-
ple, survivors and their parents often experience post-
traumatic stress disorder and anxiety, and lack of access
to behavioral health resources can have a significant, life-
long negative impact on long-term health for cancer survi-
vors.62 Partnerships between pediatric oncologists and
general pediatricians are key in advocating for both the
needs of individual patients and for the health of children
more broadly. A dedicated effort must be made to im-
prove survival, mitigate toxicities, and promote lifelong
health in all children with cancer.
CONCLUSIONS
A simplified statement of goals in pediatric oncology is to
finally “break” the survival plateau for some solid tumors
and to minimize toxicity for all children and adolescents
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diagnosed with cancer. Here, we highlighted several ways
in which innovations in drug delivery, monitoring, novel
therapeutics, and access to care continue to help move the
field of pediatric oncology forward. Children with cancer
need excellent longitudinal care both during and after com-
pletion of cancer directed therapy. Continuing to strengthen
the partnership and communication between the patient’s
pediatric oncology team and primary care pediatrician is
essential in this mission.
ABBREVIATIONS
ctDNA: circulating tumor DNA
DIPG: diffuse intrinsic pontine glioma
RWD: real world data
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